The Mechanism Study Of N-3Polyunsatured Fatty Acid On Colon Cancer Treatment

BackgroundEpidemiological studies have found that inflammation-related chronic disease incidence is relatively low in regular consumption of fish populations. Fish oil is rich in omega-3polyunsaturated fatty acids(ω-3PUFAs).ω-3PUFAs have many beneficial effects and have been widely used in prevention and treatment of various diseases. Recently, more and more empirical evidences show that ω-3polyunsaturated fatty acids have a significant beneficial effect in cancer treatment. Meanwhile, our preliminary studies in vitro and in vivo have further confirmed that omega-3polyunsaturated fatty acids can inhibit tumor cell proliferation, also can sensitize effect of chemotherapy when combined with chemotherapy drugs.Research ObjectiveIn vivo tumor-bearing mice level, we investigate the anticancer mechanism of ω-3PUFA and5-Fuorouracil (5-FU) alone or in combination in treatment of colon cancer, thus may provide new ideas for comprehensive treatment of colon cancer. in vivo tumor-bearing mice level, investigate the effect of co-3polyunsaturated fatty acid alone or combined with chemotherapy to treat the mice colon carcinomaTumor Bearing Mice MethodsIn vivo Methods:Mice colon cancer cell line (C-26) subcutaneous injected into Balb/c mice to constitute a tumor-bearing mice model, the mice were divided into four groups:Group1tumor-bearing mice without intervention; Group2tumor-bearing mice were intervened with oral fish oil; Group3mice were intervened with5FU chemotherapy; Group4tumor-bearing mice were intervened with oral fish oil and chemotherapy. Oral fish oil were pharmaceutical drugs made in Beijing BaiHui, which is high-purity (DHA, EPA>80%, ethyl ester type) soft capsules, and the mice fed with2g/kg per day applied to the surface of the mouse feed. Chemotherapy is using clinical5-FU intravenous injection, intraperitoneal injected into tumor bearing mouse every two days (20mg/kg), from the day of significant tumor generated after being subcutaneously injected with tumor cells to the day of treated mice being killed after8days’ intervention.Carefully recorded the following index:①tumor-bearing mice’ general status, food intake and body weight changes in time;②mice tumor volume changes;③At the end of experiment, extract tumor tissue RNA of each group mice, using RT-PCR method, compare the mRNA expression of tumor invasion and proliferation related gene IGF-1、IGF-2;④Extract the tumor tissue protein of each group mice, using Westernblot method to detect IGF-1、IGF-2expression in protein leverl;In vivo Results①General status, food intake and body weight changes of tumor-bearing mice:the mice intervened with oral fish oil showed generally good, no obvious symptoms; Intraperitoneal injection of5-Fu chemotherapy can significantly affect the food intake of the tumor bearing mice. With the growth of tumors, mice in each groups decreased food intake gradually, the mice’s general status deteriorated noticeably, body weight decreased, and turn out tumor cachexia symptoms. Mice intervened with oral fish oil (group2), compared with the corresponding tumor-bearing mice without intervention group (group1), the body weight loss were reduced significantly (P<0.05). Mice intervened with oral fish oil and chemotherapy (group4), compared with tumor-bearing mice intervened with5-FU chemotherapy only (group3), the body weight loss were reduced significantly(P<0.05). Oral fish oil can improve cancer cachexia.②Tumor volume changes of the tumor bearing mice:The tumor bearing mice intervened with chemotherapy (group3,4), compared with mice intervened without chemotherapy (group1,2), tumor volumes were significantly smaller (P<0.05). The tumor bearing mice intervened with oral fish oil (group3), compared with mice without intervened (group1), tumor volumes weren’t significantly different(P>0.05), and the results is the same when Mice intervened with oral fish oil and chemotherapy (group4) compared with tumor-bearing mice intervened with5-FU chemotherapy only (group3).③mRNA expression of downstream gene IGF-1、IGF-2:oral fish oil or5-FU chemotherapy inhibited tumor tissue IGF-1、IGF-2in mRNA expression (two genes in2,3,4group were significantly lower than those in group1, p<0.05), and The results of the comparison between any two groups were significant differences (p<0.05).④Tumor tissue gene IGF-1、IGF-2protein expression by Westernblot test:oral fish oil or5FU chemotherapy inhibited tumor tissue IGF-1、IGF-2expression (two genes in2,3,4group was significantly lower than that in group1, p<0.05). and The results of the comparison between any two groups were significant differences (p<0.05).Conclusion of this study1. ω-3PUFA can inhibit invasion-related gene IGF-1、IGF-2expression; Play a role in improving tumor invasion and proliferation characteristics. Combining with ω-3PUFA has some beneficial effects in cancer chemotherapy; ω-3PUFA can improve cancer cachexia.2. Compared to the significant side effects of chemotherapy drugs, co-3PUFA has all without side effects. This experimental result provides the lab basis for the further clinical application of ω-3PUFA (EPA/DHA) as an adjuvant chemotherapy added to colon cancer comprehensive treatment program.